Different effects of strength and endurance exercise training on COX-2 and mPGES expression in mouse brain are independent of peripheral inflammation

Abstract

Acute endurance exercise has been shown to modulate cyclooxygenase (COX)-2 expression, which is suggested to affect neuronal plasticity and learning. Here, we investigated the effect of regular strength and endurance training on cerebral COX-2 expression, inflammatory markers in the brain, and circulating cytokines. Male C57BL/6N mice were assigned to either a sedentary control group (CG), an endurance training group (EG; treadmill running for 30 min/day, 5 times/wk, 10 wk), or a strength training group (SG; strength training by isometric holding, same duration as EG). Four days after the last bout of exercise, blood and brain were collected and analyzed using real-time PCR, Western blot, and a multiplexed immunoassay. In EG, COX-2 mRNA expression in the cortex/hippocampus increased compared with CG. A significant increase of COX-2 protein levels was observed in both cortex/hippocampus and hypothalamus of mice from the SG. Nuclear factor (NF)κB protein levels were significantly increased in mice from both exercise groups (hypothalamus). A significant increase in the expression of microsomal prostaglandin E synthase (mPGES), an enzyme downstream of COX-2, was found in the hypothalamus of both the EG and SG. While most inflammatory factors, like IL-1α, IL-18, and IL-2, decreased after training, a positive association was found between COX-2 mRNA expression (cortex/hippocampus) and plasma IL-6 in the EG. Taken together, this study demonstrates that both endurance as well as strength training induces COX-2 expression in the cortex/hippocampus and hypothalamus of mice. A potential mediator of COX-2 expression after training might be circulating interleukin (IL)-6. However, further research is necessary to elucidate the role of inflammatory pathways on brain plasticity after training.

Immune-regulating effects of exercise on cigarette smoke-induced inflammation

“…The increased expression of COX-2 and microsomal prostaglandin E synthase, an enzyme downstream of COX-2, were independent of peripheral inflammation. 138 Exercise improved oxidative stress and inflammation directly at the brain of old high-fat-fed ApoE −/− mice, reaffirming the neuroprotective effects of exercise in a model of mice with vascular brain lesions. 138 On the other hand, aged mice, training above the lactate threshold showed increased levels of brain PGC-1α, mTOR, and phospho-mTOR protein levels, as well as citrate synthase mRNA levels.…”

“… 138 Exercise improved oxidative stress and inflammation directly at the brain of old high-fat-fed ApoE −/− mice, reaffirming the neuroprotective effects of exercise in a model of mice with vascular brain lesions. 138 On the other hand, aged mice, training above the lactate threshold showed increased levels of brain PGC-1α, mTOR, and phospho-mTOR protein levels, as well as citrate synthase mRNA levels. 139 A similar relationship has been confirmed in young mice.…”

Age Dependent Hypothalamic and Pituitary Responses to Novel Environment Stress or Lipopolysaccharide in Rats

“…This threshold can be reduced when IL-6 is combined with low doses of other cytokines such as IL-1 (Cartmell et al, 2000 ). Interestingly, low circulating IL-6 levels that also occur during exercise seem to correlate with COX2 expression in the hypothalamus (Kruger et al, 2016 ) but are not accompanied by fever.…”

The effect of different exercise training modes on dentate gyrus neurodegeneration and synaptic plasticity in morphine-dependent rats

“…Kruger et al recently reported that the COX-2 expression induction is more obvious followingstrength training[42].In summary, concurrent training prevents morphine-induced neurodegeneration via a rise in neurogenesis in the hippocampus DG of rats resulting in synaptic plasticity enhancement.Therefore, exercise training may be an appropriate novel candidate for treating opioid addiction.…”